This August, Michigan-based Grand River Aseptic Manufacturing was selected to provide support to Operation Warp Speed, the U.S. government-led expansion of capacity for manufacturing and distributing vaccines and therapeutics related to COVID-19.
The timing was right: GRAM had recently completed a 20-month expansion to triple its capacity. The company develops contract pharmaceuticals and manufacturer injectable drug products—"fill/finish,” as it is known in the industry.
GRAM entered into an agreement with Janssen Pharmaceutical Co. of Johnson &Johnson to provide the fill line to manufacture its vaccine candidate, with 100% of that line’s capacity going toward government needs.
A Novel Approach to Project Delivery
To build the expansion, GRAM partnered with design and construction firm CRB, which has over 75 vaccine facilities under its belt.
CRB’s ONEsolution approach to GRAM’s facility expansion aligned all stakeholders – GRAM leadership, design leads, construction leads, and key subcontractors—on quality, cost and schedule from initial planning through operational readiness. With everyone aligned and committed to the parameters in the beginning as a group, this approach enabled the project to be completed more quickly than typical for the pharmaceutical industry. Typically, the client determines cost and schedule, then gives those requirements to the architect and engineer, who may adjust the timeline. After the architect and engineer wrap up their part of the work, requirements are passed on to a construction manager, who manages trade partners and may add to the timeline.
The acceptable performance metric for most pharmaceutical manufacturing construction projects is plus or minus 30% on costs, with quite a wide range when it comes to scheduling. The GRAM project was completed with tighter certainty around both costs and schedules.
And time was of essence. CRB’s fast-tracking tactics—including 80% of mechanical systems prefabricated and detailed forecasting of staffing and resources--allowed for the facility’s operational turn-over, FDA validation and equipment start-up to begin months earlier than otherwise possible. GRAM began qualifications and media fills early in 2020. Production in the facility started six weeks ahead of the original schedule, which was to be end of October 2020.
The achieved timeline is as follows:
Feb 2020: Mechanical work complete. Equipment qualification.
Jul/Aug 2020: Media qualification.
Sept 2020: Partnered with a vaccine candidate producer.
Sept 2020: GMP production.
In this case, “validation” means determining that the equipment purchased to make a drug product actually does what it is intended to do so, in terms of drug formulation. Ultimately, the FDA wants assurances that the facility will create a sterile injectable drug product in an FDA-regulated Good Manufacturing Processes (GMP) facility, with appropriate equipment conforming to the process specifications.
With a vaccine candidate on the line, GRAM had to accelerate both its facility readiness and its approach to media fill qualification. The team moved swiftly to validate and qualify both the equipment and processes related to the COVID-19 vaccine candidate.
This process was complicated by travel restrictions related to containing the spread of the virus. When qualifying new equipment, equipment vendor experts typically are on site to support and train a CDMO’s staff. Once travel restrictions were implemented these activities had to go completely remote, with remaining qualifications being completed by video calls with vendors.
The Future of Post-COVID Pharmaceutical Manufacturing
According to a survey of 150 pharma industry companies conducted by CRB (CRB Horizons: Cell & Gene Therapy), viral-vector manufacturing is predicted to grow up to 20% year-over-year through 2025. (Viral vectors are a delivery vehicle used in FDA-approved gene therapies for treatment of disease and for vaccines, delivering genetic material into cells. Facilities manufacture such viral vectors for the pharmaceutical industry as components for the appropriate treatment or vaccine.)
Some 80% of survey respondents expressed concern, however, with process development and optimization in commercial manufacturing.
A new standard will be essential to build that additional capacity, and to bring back to the U.S. the development of active pharmaceutical ingredients (APIs), product formulation and packaging from countries such as China and India.
Pharmaceutical companies are transitioning from building their own, specific product facilities, to outsourcing their products to a dependable contract development manufacturing organization. To succeed, these CDMOs must be nimble and able to pivot and adapt for their client’s products. The facility was designed with flexibility so GRAM could accommodate a wide variety of clients, including any COVID-19 vaccine process being developed by various pharmaceutical companies.
The days of building new, single product facilities are largely gone. The industry is no longer designing for the manufacture of specific products. Instead, more pressure is being brought to bear to create adaptable “plug and play” facilities where products can be brought in and out according to demand.
The COVID-19 pandemic has brought greater attention to the need for domestic pharmaceutical manufacturing capabilities. What is being learned now could have strong, positive economic repercussions for the overall health of the pharmaceutical industry domestically. From the likely return of API development to the U.S., to the faster, more efficient and more effective formulation and packaging of vaccines and therapeutics, new facility design and construction techniques are marking the latest chapter in the advancement of science and medicine.